Cancer Research: Current Trends & Future Directions

Cancer Research Current Trends & Future Directions

Foreword

Throughout history, progress of humankind can be measured by the achievements and milestones of each generation’s new knowledge discoveries and their applications. Scientists, engineers, and inventors’ contributions have impacted and in most cases improved society and the human condition. Notably, given the knowledge and tools available at the time, sending men to the moon was one of these. The prevention and cure of most, perhaps all, cancer would be this century’s greatest achievement. With some cancers we have never been closer, while with others such a day currently seems unrealistic.

Discoveries in cell and molecular biology as well as biochemistry and genetics, and their application in medicine, have been the foundation for remarkable advances in health care, including cancer. To anyone who has seen the wide-ranging impact of cancer, both emotionally and financially, the goal of finishing the job – the prevention and cure of cancers - is worth the investment and causes us to consider game-changing new ways in which we might undertake this effort.

The 16th century author and scientist Sir Francis Bacon once said “knowledge itself is power.” Greg Simon, Executive Director of the White House Cancer Moonshot Task Force, when speaking at Fortune’s 2016 Brainstorm Health conference in San Diego, pointed out that, “We still live in an information-scarce medical world.”

Thanks to the hard work of researchers, doctors, nurses, healthcare professionals, and the public advocates who support their efforts, early diagnosis and sophisticated new treatments for cancer are now available, and promising new approaches are in the pipeline. But when it comes to cancer, we have had periods of hope that ultimately proved to be unfounded. There is much more to be done, especially when considering that, just in the US, two of every three men and one of every three women will face cancer of some type during their lives.

Because of its privileged position in having developed Scopus, the largest and most comprehensive database of biomedical and clinical research, Elsevier rightfully accepts the obligation to use this valuable tool to support and inform the future of cancer research. In this report, we see the global landscape of cancer research. We hope to help us all see both the forest and the trees, and hopefully a straighter pathway forward. To get where we want to go, we first must take stock in where things stand and how things function currently. In this report, Elsevier, in association with the biomedical research community, endeavors to characterize the cancer research landscape in the hope that it will provide helpful new insights.

cancer research – current trends & future directions 3 Introduction

In association with the scientific community, Elsevier has produced a number of reports that have focused on important and emerging areas of research. These include Stem Cell Research – Trends and Perspectives of the Evolving International Landscape; Brain Science – Mapping the Landscape of Brain and Neuroscience Research; and Sustainability Science in a Global Landscape.

In these cases, the full reports were written and produced prior to their open public release. In the case of this report on cancer research, we are motivated to take a different approach because of the importance and rapidly progressing nature of cancer research. Individual draft installments of the Cancer Science – Current Trends & Future Directions report will be produced and openly released for immediate use and input. Essentially, each installment is a type of pre-print that is a common practice in some disciplines and is being considered for adoption by others.

The initiative to speed up cancer research, currently called the "Cancer Moonshot," is administered through the White House. After the incoming administration devel- ops its priorities for its support for the initiative, we are looking forward to contin- uing to produce additional installments of the report. The nature and number of installments is not set and will be informed by input from the community and an advisory board. We anticipate four to six topic-specific installments plus an analytical summary. Our hope is to release the full report by end of 2017. At the same time, The Lancet Oncology, an Elsevier publication, will produce a specially com- missioned issue focused on cancer with direct contributions from leading cancer researchers that will be published during the summer of 2017.

The report is being developed with Elsevier’s Research Intelligence products and services; research performance data comes from the Scopus database, which is approaching 1 million peer-reviewed publications and scientific proceedings on cancer research produced in the past decade.

When completed, and in combination with other materials, this report on cancer research will offer the research community, the public, policy makers, and research funding organizations information at a new level of assessment on the current state of cancer related research. We hope that this will be used to inform the development of new operational approaches, policies, and funding strategies at the laboratory, institutional, national, and international levels.

cancer research – current trends & future directions 4 Preface & Context

This report is prepared and openly distributed by Elsevier as a service to the research community, policy makers, research funders, and the public.

Elsevier’s Research Intelligence collection of solutions is focused on providing objective analytical insights derived from the highest quality data available. This work is based on the Scopus database that is approaching 1 million peer-reviewed publications and scientific proceedings on the topic of cancer research produced in the past decade.

The goal is to inform the selection of approaches, priorities, and strategies in order to produce new knowledge that will address the key challenges related to cancer research in the most effective, efficient, and impactful way possible.

This first instalment presents an overarching view of emerging trends, many of which will be examined in greater detail in subsequent instalments. The maps present the key countries and institutions which form the basis for analysis in this document.

cancer research – current trends & future directions 5 Cancer Research Output, Growth, and Impact in Canada selected countries publications growth fwci

4,653 8.29% 1.89

US publications growth fwci

34,674 6.59% 1.88

UK publications growth fwci

7,122 6.13% 2.08

France publications growth fwci

5,023 8.16% 1.93

Map of countries leading in cancer research output along with publication output, publication growth, and field-weighted citation impact (FWCI). World average (indicated by dashed circles) for publication growth: 9.93% / World average for field-weighted citation impact: 1.00. Data for publication output and field-weighted citation impact: 2014 / Data for publication growth: 5-year period (2010 – 2014). Source: Scopus

cancer research – current trends & future directions 6 Japan publications growth fwci

8,001 6.16% 1.05

China publications growth fwci

20,505 25.13% 1.26

Germany publications growth fwci

6,540 6.61% 1.93

Italy publications growth fwci

6,011 9.36% 2.07

cancer research – current trends & future directions 7 University of Michigan Cancer Research Output Ann Arbor, MI and Impact of top cancer publications citations fwci research institutions 4,390 88,240 2.74

Mayo Clinic Rochester MN Rochester, MN publications citations fwci

3,867 86,902 3.17

University of British Columbia Vancouver, BC publications citations fwci

3,265 80,461 3.11

University of California at San Francisco San Francisco, CA publications citations fwci

4,068 120,545 3.47

University of California at Los Angeles Los Angeles, CA publications citations fwci

3,828 83,685 3.01

Karolinska Institutet Solna, Sweden publications citations fwci University of Texas MD Anderson Cancer Center 3,958 76,583 2.69 Houston, TX publications citations fwci

10,273 208,253 2.60 Map of top cancer research institutes along with publication output, count of citations, and field-weighted citation impact (FWCI) 2011 – 2015. World average for field-weighted citation impact: 1.00. Source: Scopus

cancer research – current trends & future directions 8 University of Toronto Toronto, ON publications citations fwci

6,644 114,192 2.43 Harvard University Cambridge, MA publications citations fwci University of Pittsburgh Pittsburgh, PA publications citations fwci 13,029 344,030 3.50

3,807 78,806 2.71

Dana-Farber Cancer Institute Boston, MA publications citations fwci

3,202 118,953 4.62

Memorial Sloan Kettering Cancer Center New York City, NY publications citations fwci

6,496 174,470 3.62

University of Pennsylvania Philadelphia, PA publications citations fwci

4,122 84,497 2.85

Johns Hopkins University Baltimore, MD publications citations fwci National Institutes of Health Bethesda, MD 6,236 149,979 3.21 publications citations fwci

8,842 195,329 2.70

based on map from wikipedia / nuclearvacuum / cc by-sa 3.0

cancer research – current trends & future directions 9 ► Cancer research encompasses a broad array of re- led to the expansion of the vaccine recommendation to search and includes a diverse range of specific research young men and boys as well. This single advance has cut topics. Within this report, cancer research is defined as cervical cancer risk, making it one of the most prevent- research where the published results include ‘cancer’ or able cancers. Similarly in 2001, Imatinib (Gleevec) was ‘oncology’ within the title, abstract, or list of keywords of approved for the targeted treatment of a rare chronic the publications, as indexed in the Scopus database. This myelogenous leukemia. By attacking specific molecular includes all publication types, namely articles, reviews, defects in patients while successfully sparing healthy conference papers, book chapters, notes, letters, short cells, this treatment transformed a rare deadly cancer surveys, editorials, articles in press, erratum, books, from being a disease with an acute three to five year life conference reviews, business articles, and abstract re- expectancy, into a more chronic long-term, manageable ports. Articles represent 77% of the research, and reviews condition. Despite such advances, the impact of cancer represent 14% of the publications retrieved. The coun- remains high and the number of cases is projected to tries selected for analysis produce the highest number of nearly double over the next twenty years as the global cancer research publications in 2014. Top cancer research population ages 3. institutions were identified by selecting the institutions with the highest number of citations in cancer research ► Analysis of cancer research reveals that the US hosts a over the period 2011-2015. large fraction of the world’s leading cancer research institutions 4 (see Cancer Research Institutions Map) and can- In 2014, cancer research represents over 4 % of all re- cer research output from the US represents the largest search performed globally, reflecting the huge amount of share of global output in the field (see Figure 1). The US effort that has been invested worldwide to address this share of cancer research has been declining over the past multifaceted and complex disease. Today it is the leading decade. This is largely the result of significant increase cause of premature death in 28 European countries 1 in China’s cancer research publication output, which and across the United States (US) 2. Worldwide, cancer constitutes 17% of the global publication share in 2014, research output has increased year on year over the past up from 5% in 2005 (see Figure 1). The impact of cancer decade and has seen notable advances in our under- research, which can be examined via field-weighted standing, diagnosis, and treatment of this disease. For citation impact 5 (FWCI), has risen over the past decade example, to date, the US Food and Drug Administration for most of the countries included in this analysis. China has approved two vaccines (Gardasil, and later Cervar- has seen a particularly large increase in FWCI from just ix) against Human Papilloma Virus (HPV), a virus that above 0.5 in 2005 to above 1.2 in 2014. Japan, France, can cause cervical cancer in women. While initially the Germany, Italy, and the UK have also seen an overall in- vaccines were only approved for young women and girls, crease in FWCI over the past decade while the FWCI for research that linked HPV to a variety of other cancers US cancer research has been stable over the past decade.

Figure 1 — Change in publication share and citation record over the past decade for selected countries (2005 – 2014). Source: Scopus

2.5 Canada France

2.0 UK US

1.5 Germany Italy China Japan 1.0 World average (= 1.0) field-weighted citation impact citation field-weighted

0.5 0% 5% 10% 15% 20% 25% 30% 35% 40% global publication share

cancer research – current trends & future directions 10 ► The US is the most prolific producer of cancer research (see Figure 2). US researchers have dominated research production for the past decade, producing more publications per annum than Japan, the UK, France, Germany, and Italy combined.

The volume of US cancer research publications has actu- ally increased year on year and it is due to other countries, notably China, rapidly increasing output that the global publication share belonging to the United States has declined (Figure 2). In 2014, China produced approx- imately the same volume of papers as the US did in 2005.

Figure 2 — Number of Cancer Research publications for selected countries (2005 – 2014). Source: Scopus

35,000 US

30,000

25,000

China 20,000

15,000

10,000 Japan UK

number of publications in cancer research number of publications Germany Italy 5,000 France Canada

0 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

1 Leading causes of death in Europe: fact sheet, WHO Europe. 2 http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf 3 WHO Fact sheet N°297, updated February 2015. 4 ‘Top’ institutions were identified by selecting the institutions with the highest number of citations in cancer research over the period 2011 – 2015. 5 Field Weighted Citation Impact (FWCI) indicates how the number of citations received by publications compares with the average number of citations received by all other similar publications indexed in the Scopus database. It corrects for factors such as the typical citation pattern for that discipline (some disciplines have a stronger culture of citation), the age of the papers (older papers have more time to accrue citations), and their document types (typically, reviews are cited more than articles). A field-weighted citation impact of 1 indicates that the publications have been cited at the world average for similar publications, while a value of 2 indicates they have been cited twice as many times as expected.

cancer research – current trends & future directions 11 ► Increases in publication output are part of a global trend across all disciplines. Countries in this report see compound annual growth rates 6 (CAGR) in research output between 2-6%, with the exceptions of Japan (CAGR less than 1%) and China (CAGR greater than 12%) (see Figure 3). Medical research however, has been expanding at a more rapid rate than other research fields with growth rates typically 1.5 to 3 times higher than the equivalent figure for all output in the country. Cancer research follows a similar trend to medical research overall but with slightly lower growth rates, particularly in the US, Germany, and Japan. China is the only country where growth in cancer research exceeds the rate of growth for medicine.

Figure 3 — Compound Annual Growth Rate of publications in Cancer Research, Medicine, and All Disciplines in selected countries (2005 – 2014). Source: Scopus

Cancer Research Medicine All disciplines

compound annual growth rate 22.70% China 18.67% 12.34% 8.90% Canada 10.57% 4.14% 8.39% Italy 9.38% 5.69% 7.34% France 7.76% 3.83% 6.58% UK 8.23% 4.07% 6.12% US 8.61% 2.66% 5.97% Germany 8.17% 3.71% 4.52% Japan 6.85% 0.36%

6 Compound annual growth rate (CAGR) is defined as the year-over-year constant growth rate over a specified period of time. Starting with the first value in any series and applying this rate for each of the time intervals yields the amount in the final value of the series.

cancer research – current trends & future directions 12 ► Relative activity indices 7 reflect on whether research- Overall, the relative prioritization of cancer research ers in a country are focusing more attention on one dis- compared to all other disciplines is particularly high cipline than another when compared to other countries in Japan, Italy, and the US, a pattern which has been globally. A value above 1 indicates more emphasis on true throughout the past decade. At the other end of the that discipline compared to the global average. A rising spectrum are the UK and Germany, with lower relative relative activity index reflects increasing prioritization activity indices and a slow decline over the past decade. over time compared to the global average. This informa- This may reflect a more balanced research portfolio. Of tion provides important context as to whether trends are note, cancer research within the UK and Germany has general worldwide or specific to a country or group of maintained a high FWCI over the past decade irrespec- countries. tive of changes in relative activity index.

Except for China, all countries analyzed have a stable relative activity index over the decade, reflecting no change in focus on cancer research relative to global av- erages in each country over the past decade (see Figure 4). China has seen the greatest increase in relative activity index for cancer research.

Figure 4 — Relative activity index of Cancer Research against all disciplines (2005 – 2014). Source: Scopus

1.8

1.6 Japan 1.4 Italy US 1.2 Canada France 1.0 World average (= 1.0) China Germany 0.8 UK

0.6 relative activity index activity relative 0.4

0.2

0 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

7 The relative activity index is equal to the proportion of a country’s publications in Cancer Research within all disciplines divided by the proportion of the world’s publications in Cancer Research within all disciplines. The world average is 1. Above 1 means more focus/interest in Cancer Research than the global average.

cancer research – current trends & future directions 13 ► Key terms or phrases appearing in cancer research Figure 5 (next page) — Top 50 Key Phrases in Cancer Research publications over the past 5 years can provide a high worldwide (left) and for the US (right), 2011 – 2015. level view of areas of focus. Figure 5 provides a graphical Source: Scopus depiction of the ‘hot topics’ or key phrases in cancer research globally and in the US. The frequency of the A A A Relevance of key phrase Growing Declining term or phrase is reflected by the font size in the figure. To avoid bias, the charts are presented without impos- ing additional filters and as a result, some general terms naturally appear. The majority of key phrases appear in both US and global research, possibly as a result of the large share of cancer research represented by US publications. Also the majority of terms appear to be increasing over the past 5 years, reflecting the increased importance of cancer research.

Over the past 5 years there has been increasing emphasis on early detection of cancer, neoplastic stem cells, microRNAs, and biological markers. Compared with global research, the US has increased emphasis on de- veloping immunotherapies, xenograft models, and stud- ies of the tumor microenvironment. In contrast, terms such as ‘general surgery,’ ‘recurrence,’ and ‘lymph nodes’ appear exclusively among the top 50 for global cancer research. There were also interesting differences with regards to the types of cancer dominating the research focus in the US compared to globally. The key phrases melanoma, head and neck neoplasms, and thyroid neoplasms were exclusive to the US top 50 key phrase list while stomach neoplasm, hepatocellular carcinoma, and rectal neoplasm were exclusive to the global top 50 key phrase list. Additionally, while both the global and US top 50 lists include the term ‘prostatic neoplasm,’ the US list includes 3 additional terms related to prostate health: ‘prostate-specific antigen,’ ‘prostatectomy,’ and ‘prostate,’ suggesting a high relative importance of this topic within cancer research in the US.

cancer research – current trends & future directions 14 ↓ World USA ↓

Neoplasms1 Breast Neoplasms 2 Breast Neoplasms Patients 3 Prostatic Neoplasms Prostatic Neoplasms 4 Patients Cells 5 Cells Colorectal Neoplasms 6 Therapeutics Therapeutics 7 Colorectal Neoplasms Neoplasm Metastasis 8 Early Detection of Cancer Lung Neoplasms 9 Risk Carcinoma, Non-Small-Cell Lung 10 Survival Survival 11 Lung Neoplasms Stomach Neoplasms 12 Neoplasm Metastasis Risk 13 Carcinoma, Non-Small-Cell Lung Drug Therapy 14 Radiation MicroRNAs 15 Ovarian Neoplasms Apoptosis 16 Pancreatic Neoplasms Early Detection of Cancer 17 MicroRNAs Carcinoma 18 Drug Therapy Prognosis 19 Survivors Radiotherapy 20 Breast Ovarian Neoplasms 21 Women Pancreatic Neoplasms 22 Neoplastic Stem Cells Breast 23 Mutation Uterine Cervical Neoplasms 24 Disease Adenocarcinoma 25 Biological Markers Genes 26 Prostate Radiation 27 Pharmaceutical Preparations Carcinoma, Squamous Cell 28 Adenocarcinoma General Surgery 29 Xenograft Model Antitumor Assays Diagnosis 30 Immunotherapy Biological Markers 31 Melanoma Women 32 Molecular Targeted Therapy Urinary Bladder Neoplasms 33 Genes Pharmaceutical Preparations 34 Head and Neck Neoplasms Meta-Analysis as Topic 35 Urinary Bladder Neoplasms Colonic Neoplasms 36 Carcinoma Neoplastic Stem Cells 37 Prostate-Specific Antigen Mutation 38 Receptor, Epidermal Growth Factor Receptor, Epidermal Growth Factor 39 Apoptosis Recurrence 40 Humans Disease 41 Tumor Microenvironment Carcinoma, Hepatocellular 42 Uterine Cervical Neoplasms Tissues 43 Antineoplastic Agents Humans 44 Radiotherapy Cell Line 45 Tissues Lymph Nodes 46 Colonic Neoplasms Esophageal Neoplasms 47 Prostatectomy Rectal Neoplasms 48 Carcinoma, Squamous Cell Tumor Markers, Biological 49 Diagnosis Disease-Free Survival 50 Thyroid Neoplasms

cancer research – current trends & future directions 15 ► Beyond volume of research published, the quality Changes in metrics over time can be particularly in- and influence of the work produced is perhaps of great- formative, especially when paired with an understanding er importance. Looking at volume data in isolation risks of shifts in research funding priorities and public policy. missing the important consideration of the influence of Sustained improvements in quality can be harder to at- the output and fails to recognize the importance of the tain than increased volume alone, and it is interesting to spread of discoveries over time. put them in a wider context to learn about the settings that may be conducive to their emergence. In many cases, resources are required to drive and accelerate the impact of research beyond publication if A country’s field-weighted citation impact (FWCI) a positive impact is to be achieved for wider society. As reflects citations to research of (for instance) a country, a result, considerations of metrics which can reflect this compared to the world average, and corrected for factors effort become imperative. such as the typical citation pattern for that discipline (the culture of citation differs across disciplines), the age It is now possible to consider the use and impact of of the papers (older papers have more time to accrue research post publication through analyses of: citations), and their document types (typically, reviews are cited more than articles). It is a proxy for the impact a) Citations by other academics, as evidence of influ- of specific research in that field, as far as this can be ence and academic impact of the work; reflected by citation data. An FWCI equal to 1 represents a citation record equal to the world average. b) Frequency with which publications are viewed, to consider the broader reach of publications; In most countries analyzed in this report, cancer research represents a stand-out area for the country com- c) Citations of research in patents, as evidence of use of pared both to medical research and to all other disci- research in the innovation ecosystem. plines 8 (see Figure 6), as demonstrated by superior FWCI.

Figure 6 — Field-weighted citation impact in Cancer Research, Medicine and all disciplines for selected countries in 2014. Source: Scopus

Cancer Research Medicine All disciplines

field-weighted citation impact, 2014 2.08 UK 1.63 1.57 2.07 Italy 1.49 1.53 1.93 Germany 1.47 1.44 1.93 France 1.45 1.33 1.89 Canada 1.58 1.48 1.88 US 1.45 1.45 1.26 China 0.98 0.86 1.05 Japan 0.92 0.99 World average (= 1.0)

8 Japan is the exception, where the difference between cancer research, medicine and other disciplines is less marked.

cancer research – current trends & future directions 16 ► Some countries such as Germany, the UK, and most ► It is also possible to assess ‘excellence’ rather than noticeably China, show a general increase in impact over impact of the field as a whole, in this case through the the period 2005 – 2014 (see Figure 7). The US by contrast proxy of publications in the top 10% of all cited pub- displays a relatively static performance, likely as a result lications worldwide (see Figure 8). The US in 2014 for of the large volume of publications represented by US example has 30% of its publications in the top 10% output. worldwide. While this performance is strong, it is slightly down from 2005 as other countries have increased their excellent output at a faster rate.

China’s rise in top cited publications has been remarkable, particularly between 2007 and 2012, and also mir- rors its general increase in FWCI over the period.

Figure 7 — Field-Weighted Citation Impact for Cancer Research in selected countries (2005 – 2014). Source: Scopus 2.5

UK Italy 2.0 France Germany Canada US 1.5

China World average (= 1.0) Japan 1.0

field-weighted citation impact citation field-weighted 0.5

0 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Figure 8 — Proportion of Cancer Research Publications that are in the top 10 citation percentile for comparator countries (2005 – 2014). Source: Scopus 40%

35% Italy UK US 30% Germany Canada 25% France China 20% Japan 15%

10%

5% proportion in the top 10 citation percentile 10 citation in the top proportion 0% 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

cancer research – current trends & future directions 17 Table 1 — Most cited publications in Cancer Research published in the period 2010 – 2014. Note that older publications have more time in which to be cited. Source: Scopus

Title Authors Year Source title Citations

Hallmarks of cancer: The next generation Hanahan D., Weinberg R.A. 2011 Cell 12,595

International Estimates of worldwide burden of cancer Ferlay J. et al. 2010 Journal of 7,984 in 2008: GLOBOCAN 2008 Cancer

New England Improved survival with ipilimumab in Hodi F.S. et al. 2010 Journal of 4,327 patients with metastatic melanoma Medicine

New England Improved survival with vemurafenib in Chapman P.B. et al. 2011 Journal of 3,316 melanoma with BRAF V600E mutation Medicine

The genome analysis toolkit: A MapReduce Genome framework for analyzing next-generation McKenna A. et al. 2010 3,046 Research DNA sequencing data

Global and regional mortality from 235 causes of death for 20 age groups in 1990 Lozano R., Naghavi M., 2012 The Lancet 2,925 and 2010: A systematic analysis for the Foreman K., et al Global Burden of Disease Study 2010

New England Safety, activity, and immune correlates of Topalian S.L. et al. 2012 Journal of 2,825 anti-PD-1 antibody in cancer Medicine

Management of hepatocellular carcinoma: Bruix J., Sherman M. 2011 Hepatology 2,724 An update

Grivennikov S.I., Greten Immunity, Inflammation, and Cancer 2010 Cell 2,477 F.R., Karin M.

Comprehensive molecular portraits of Koboldt D.C., Fulton R.S., 2012 Nature 2,457 human breast tumours McLellan M.D., et al

Intratumor heterogeneity and branched New England evolution revealed by multiregion Gerlinger M. et al. 2012 Journal of 2,342 sequencing Medicine

New England Anaplastic lymphoma kinase inhibition in Kwak E.L. et al. 2010 Journal of 2,323 non-small-cell lung cancer Medicine

cancer research – current trends & future directions 18 Title Authors Year Source title Citations

New England Gefitinib or chemotherapy for non-small- Maemondo M. et al. 2010 Journal of 2,181 cell lung cancer with mutated EGFR Medicine

New England Sipuleucel-T immunotherapy for Kantoff P.W. et al. 2010 Journal of 2,174 castration-resistant prostate cancer Medicine

MTOR signaling in growth control and Laplante M., Sabatini D.M. 2012 Cell 2,129 disease

A roadmap for graphene Novoselov K.S. et al. 2012 Nature 2,122

New England Reduced lung-cancer mortality with low- Aberle D.R. et al. 2011 Journal of 2,110 dose computed tomographic screening Medicine

Integrated genomic analyses of ovarian Bell D. et al. 2011 Nature 2,104 carcinoma

Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced Bang Y.-J. et al. 2010 The Lancet 2,061 gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial

New England Inhibition of mutated, activated BRAF in Flaherty K.T. et al. 2010 Journal of 2,018 metastatic melanoma Medicine

cancer research – current trends & future directions 19 ► Impact based on a different metric, ‘field weight- Italy is the only country to show a notable increase ed views impact’ (FWVI) relates to the electronic in FWVI, while relative views for Canada and the views of publications online. Like FWCI, FWVI is US dipped slightly. China does not see the rise in corrected for the field, age, and type of publications. views seen in the citation data. However, unlike citations, which can take a long time to accrue, the measure of views provides a more Recapping the citation data shown in Figure 7 to immediate indication of how much publications permit comparison with FWVI, Figure 9 Panel B are being accessed. It also provides insights into shows that the US and Canada were the strongest usage beyond the academic and scholarly sphere, for performers with respect to citations in 2005-2009. instance by practitioners or students. For all coun- The UK, France, Germany, and Italy have increased tries except China and Japan, views of publications their citation impact in cancer research relative on cancer research are higher than the global average to the world over the last 5 years and now have a for cancer research (equal to a FWVI of 1) (see Figure similar record to US and Canada. China shows the 9, panel A). There is a slightly different pattern over most rapid improvement and notably moved from time for views than for citations (see Figure 9, panel B). below to above world average in the time period.

Figure 9 — Field-weighted citation impact and field-weighted views impact for Cancer Research in selected countries for two time periods: 2005 – 2009 & 2010 – 2014. Source: Scopus

2010 – 2014 2005 – 2009 World average (= 1.0)

Panel A Panel B Field-Weighted Views Impact Field-Weighted Citation Impact

Canada Canada

2.0 2.0 US China US China 1.5 1.5

1.0 1.0

0.5 0.5

UK 0.0 France UK 0.0 France

Japan Germany Japan Germany

Italy Italy

cancer research – current trends & future directions 20 ► Citation of publications in patents can give an indication of the utility of research in supporting new innova- tions. Interestingly, publications in cancer research are far more likely to be cited in patents than publications in medicine overall (see Figure 10). In most countries cancer research sees at least double the rate of citation in patents compared to publications in medicine.

The US has the highest rate of patent citations across all fields, closely followed by Germany, Canada, and the UK. This is likely to be at least partly reflective of the US patenting and research culture but may also reflect on as- pects such as collaborations, quality, and type of research produced. The citations of publications in patents will be explored in greater detail in subsequent reports.

Figure 10 — Patent Citations per publication in Cancer Research, Medicine, and All Disciplines for selected countries in 2010. Source: Scopus

Cancer Research Medicine All disciplines

patent citations per publication 0.32 US 0.14 0.11 0.28 Germany 0.12 0.09 0.26 Canada 0.09 0.07 0.25 UK 0.10 0.07 0.22 Italy 0.10 0.07 0.22 France 0.10 0.07 0.17 Japan 0.09 0.08 0.13 China 0.06 0.03

cancer research – current trends & future directions 21 ► 'Top' institutions in cancer research were identified Harvard and the Dana-Farber Institute 10 lead with the by selecting the institutions with the highest number of highest volume and highest FWCI respectively. Com- citations in cancer research 9. This metric partly reflects bined, they produce over 21,000 publications from 2011- volume of research and partly the reach and quality of 2015 (see Figure 11). They also have some of the highest that output. A map of the top institutions can be found growth rates of publication output over the period. pages 10-11. The majority of institutions identified through this metric are based in North America.

Among the top 10 cancer research institutions, all institutions have a field-weighted citation impact (FWCI) more than twice that of the world average and all produced over 3,000 cancer research publications from 2011-2015 (see Top Cancer Research Institutions Map).

Figure 11 — Top institutions in cancer research and their publication volume and citation performance over the past decade (2005 – 2014). Bubble size is proportional to the growth in publication output over the period by compound annual growth rate (CAGR). Source: Scopus

4.5

Dana-Farber Cancer Institute 4.0

2014 3.5

– University of Memorial Sloan Kettering California at Harvard University San Francisco Cancer Center Mayo Clinic 3.0 Rochester MN Johns Hopkins University

University of Michigan National Institutes of Health 2.5 University of Texas University of Toronto MD Anderson Cancer Center

2.0

field-weighted citation impact, 2005 impact, citation field-weighted 1.5

World average (= 1.0) 1.0 0 5,000 10,000 15,000 20,000 25,000 scholarly output, 2005 – 2014

9 Over the period 2011 – 2015. 10 The Dana-Farber Cancer Institute is a teaching affiliate of Harvard Medical School.

cancer research – current trends & future directions 22 ► Consistency of research impact over time is an important factor. All top cancer institutions analyzed have an FWCI of 2 or greater for the years shown and many show a trend of improvement over time towards the present day (see Figure 12).

Figure 12 — Field-weighted citation impact for top institutions in Cancer Research in 2005, 2010 and 2014. Source: Scopus

2014 2010 2005

field-weighted citation impact 4.13 Dana-Farber Cancer Institute 4.27 3.81

Memorial Sloan Kettering 3.62 3.61 Cancer Center 2.35 3.45 Harvard University 3.14 2.80

University of California 3.03 2.96 at San Francisco 2.02 2.99 Johns Hopkins University 2.45 2.66

University of Texas 2.73 2.40 MD Anderson Cancer Center 2.00 2.69 University of Michigan 2.18 2.16 2.66 Mayo Clinic Rochester MN 2.95 2.93 2.49 National Institutes of Health 2.47 2.45 2.11 University of Toronto 2.09 2.43

cancer research – current trends & future directions 23 ► Top cancer research institutions are disproportion- ately likely to produce top cited publications in their output (see Figure 13). The proportion of their output that is in the top 1% of cited publications worldwide is a means to assess this relationship. In 2014, for the Da- na-Farber Cancer Institute over 18% of their output was in the top 1% of cited publications globally.

Figure 13 — Proportion of all publications in top 1 citation percentile for top cancer institutions in 2005, 2010 and 2014. Source: Scopus

2014 2010 2005

output in top 1 citation percentile 18.6% Dana-Farber Cancer Institute 15.1% 13.3%

Memorial Sloan Kettering 12.6% 10.9% Cancer Center 9.4% 11.7% Harvard University 11.9% 10.6% 10.4% Johns Hopkins University 7.2% 7.9%

University of California 9.7% 10.0% at San Francisco 7.2%

University of Texas 9.5% 8.0% MD Anderson Cancer Center 7.0% 8.4% University of Michigan 5.9% 7.1% 7.9% Mayo Clinic Rochester MN 7.8% 8.4% 7.1% National Institutes of Health 7.7% 8.6% 6.0% University of Toronto 4.5% 6.6%

cancer research – current trends & future directions 24 ► Patent citations per publication are also highest for the Dana-Farber Cancer Institute, Harvard University, and the University of California at Los Angeles, mirroring the top three institutes with the highest proportion of publications in the top 1% of cited cancer publications (see Figure 14).

Figure 14 — Patent citations per publication for top institutions in Cancer Research, Medicine and All Disciplines in 2010. Source: Scopus

Cancer Research Medicine All disciplines

patent citations per publication, 2010 1.11 Dana-Farber Cancer Institute 0.78 0.97 0.55 Harvard University 0.20 0.24 0.39 National Institutes of Health 0.30 0.37

University of California 0.36 0.15 at San Francisco 0.20

Memorial Sloan Kettering 0.36 0.25 Cancer Center 0.28 0.35 Johns Hopkins University 0.14 0.15 0.31 University of Toronto 0.11 0.11 0.30 University of Michigan 0.12 0.12

University of Texas 0.27 0.25 MD Anderson Cancer Center 0.27 0.24 Mayo Clinic Rochester MN 0.15 0.16

cancer research – current trends & future directions 25 Glossary of Terms

Activity index Activity index is defined as a country’s share of its total article output across subject field(s) relative to the global share of articles in the same subject field(s). For example, in 2012, the US published 4.98% of its articles in Cancer, while globally this subject field represents 3.71% of all articles published. The Activity Index for the US in Cancer in 2012 is therefore 4.98%/3.71% = 1.34. A value of 1.0 indicates that a country’s research activity in a field corresponds exactly with the global activity in that field; higher than 1.0 implies a greater emphasis while lower than 1.0 suggests a lesser focus.

Article Article (unless otherwise indicated) denotes all publication types, namely articles, reviews, conference papers, book chapters, notes, letters, short surveys, editorials, articles in press, erratum, books, conference reviews, business articles, and abstract reports.

Article output Article output for a country is the count of articles with at least one author from that country (according to the affiliation listed in the authorship byline). All analyses make use of ‘whole’ rather than ‘fractional’ counting: an article representing international collaboration (with at least two different countries listed in the authorship byline) is counted once each for every country listed.

Citation Citation is a formal reference to earlier work made in an article or patent, frequently to other journal articles. A citation is used to credit the originator of an idea or finding and is usually used to indicate that the earlier work supports the claims of the work citing it. The number of citations received by an article from subsequently-published articles is a proxy of the quality or importance of the reported research.

Compound Annual Compound Annual Growth Rate (CAGR) is defined as the year-over-year constant Growth Rate (CAGR) growth rate over a specified period of time. Starting with the first value in any series and applying this rate for each of the time intervals yields the amount in the final value of the series.

1 CAGR (t0, tn) = (V (tn) / V (t0)) — – 1 tn – t0

V (t0) : start value V (tn) : finish value tn – t0 : number of years

Field Weighted Citation Field Weighted Citation Impact (FWCI) is an indicator of mean citation impact, and Impact (FWCI) compares the actual number of citations received by an article with the expected number of citations for articles of the same document type (article, review, or conference proceedings paper), publication year, and subject field. Where the article is classified in two or more subject fields, the harmonic mean of the actual and expected citations rates is used. The indicator is therefore always defined with reference to a global baseline of 1.00 and intrinsically accounts for differences in citation accrual over time, differences in citation rates for different documents types (e.g. reviews typically attract more citations than research articles), as well as subject-specific differences in citation frequencies overall and over time and document types. It is one of the most sophisticated bibliometric indicators.

cancer research – current trends & future directions 26 The Field-Weighted Citation Impact (FWCI) for a set of N publications is defined as: N 1 cᵢ FWCI – – N eᵢ i = 1 cᵢ = citations received by publication i

eᵢ = expected number of citations received by all similar publications in the publication year plus following 3 years.

When a similar publication is allocated to more than 1 discipline, the harmonic mean is used to calculate eᵢ. For a publication i that is part of 2 disciplines:

1 1 1 1 – – (– – )+ eᵢ 2 eA eB

eA, eB = fractional counts of publications and citations, so that publication i will be counted as 0.5 publications in each of eA and eB, and the citations it has received will also be shared between A and B.

Field Weighted Views Field Weighted Views Impact (FWVI) is an indicator of mean usage, and compares the Impact (FWVI) actual number of electronic views of an article with the expected number of views of articles of the same document type (article, review, or conference proceeding paper), publication year, and subject field. Where the article is classified in two or more subject fields, the harmonic mean of the actual and expected view rates is used. The indicator is therefore always defined with reference to a global baseline of 1.00 and intrinsically accounts for differences in views accrual over time, differences in view rates for different documents types (e.g. reviews typically attract more citations than research articles), as well as subject-specific differences in viewed frequencies overall and over time and document types. The principles applied to the calculation of FWVI are the same as those for calculating FWCI.

Global publication share Global publication share is the share of publications for a specific region expressed as a percentage of the total world output. Using articles share in addition to absolute numbers of articles provides insight by normalizing for increases in overall growth of the world’s research.

Publication output Publication output is the number of publications per country, which have at least one author affiliated to an institute in that country. A publication which is co-authored by authors from different countries, thus counts towards the publication output of each country.

cancer research – current trends & future directions 27 The report was designed for online and print by CLEVER°FRANKE (www.cleverfranke.com).